TR&D 1 - Experimental design in solution NMR spectroscopy Summary A major effort of the Center on Macromolecular Dynamics by NMR Spectroscopy (CoMD/NMR) will capitalize on and extend the dramatic advances in solution NMR methods for characterizing macromolecular conformational dynamics that have occurred over the past 25 years. TR&D1 has three major foci: (i) spin relaxation for fast (ps-ns) internal dynamics and overall rotational diffusion, (ii) chemical exchange for s-ms internal dynamics and interaction kinetics, and (iii) residual dipolar coupling constants, scalar coupling constants, and chemical shifts that report averaging over conformational distributions on time scales faster than 1/??, where ?? is the variation in the given parameter between conformations. Experimental and analytical methods in all three areas will be developed with a focus on application to the really challenging protein and nucleic acid targets with complex dynamics and large molecular masses represented by the Driving Biomedical Projects. This TR&D will be strongly integrated to the other three TR&D components of CoMD/NMR, through synergistic applications with relaxometry in TR&D2 and solid-state NMR in TR&D3 as well as through tight integration with software development in TR&D4.